HIV dementia (HIV-D) and HIV-associated sensory neuropathy (HIV-SN) are the most common neurological manifestations of advanced HIV infection. The prevalence of HIV-D and HIV-SN in Sub- Saharan Africa where the majority of HIV cases reside globally is largely unknown. In addition, HIV subtype may have an impact on HIV disease progression, suggesting the possibility that HIV subtypes may differ with respect to their ability to cause neurological disease. The project will assemble a cohort of HIV+ individuals in Uganda: 1) to determine the prevalence of and risk factors associated with HIV-D and HIV-SN among untreated HIV+ individuals with moderate advanced immunosuppression, 2) to determine whether untreated HIV+ individuals decline from baseline in neuropsychological test performance, and peripheral nerve function, and 3) to obtain preliminary data to determine whether HIV subtypes differ with respect to the risk of HIV-D and HIV-SN, and progression of HIV-associated cognitive impairment and peripheral nerve function. We propose one of the first large scale prospective studies of HIV-D and HIV-SN in Sub-Saharan Africa. This proposal will provide the data necessary to characterize the prevalence and progression of HIV-D and HIV-SN, which could be used for future R01 applications. HIV-associated cognitive impairment is currently not an indication for HAART initiation in HIV+ individuals with a CD4 count in the 201-350 cells/[unreadable]L range. Our proposal will provide the data necessary to determine if clinical practice parameters for the initiation of HAART among HIV+ individuals with moderate immunosuppression and mild neurocognitive impairment should be changed in countries within Sub-Saharan Africa such as Uganda. Our proposal will examine whether HIV subtypes may differ with respect to their ability to cause HIVassociated CNS and PNS dysfunction. The proposal will also provide training for the HIV clinician-scientists in Kampala, Uganda in research studies of HIV-associated neurological disease. Based upon our preliminary data, we believe that HIV-D and HIV-SN are frequently unrecognized complications of advanced HIV infection in Sub-Saharan Africa, and are a significant cause of morbidity in HIV+ individuals in Uganda, which if identified early, can be treated effectively with antiretroviral therapy and symptomatic therapies. PUBLIC HEALTH RELEVANCE: The epidemiology of HIV dementia (HIV-D) and HIV-associated sensory neuropathy (HIV-SN) in Sub-Saharan Africa where the majority of HIV cases reside globally is largely unknown. The project will assemble a cohort of HIV+ individuals in Uganda: 1) to determine the prevalence of and risk factors associated with HIV-D and HIV-SN among untreated HIV+ individuals with moderate-advanced immunosuppression, 2) to determine whether untreated HIV+ individuals decline from baseline in neuropsychological test performance, and peripheral nerve function, and 3) to obtain preliminary data to determine whether HIV subtypes differ with respect to the risk of HIV-D and HIV-SN.